The AMP-AD Wall Of Targets

Goal

Create a visual dashboard and integrative analysis platform that provides consistent and robust supporting evidence for use in:

• Prioritization of targets nominated by individual AMP-AD projects.
• Nomination of targets supported across AMP-AD projects.
• Compilation of AMP-AD evidence for use by research community to evaluate other targets of interest.

Approach

1. Develop prototype.
2. Build alpha platform based on user feedback, focusing on gene-based queries for nominated AMP-AD targets.
3. Expand to include genes across the transcriptome (partnership with Josh Shulman @ Baylor).
4. Expand to provide entry points based on gene, protein, network, or variant queries.

Anticipated users: AMP-AD consortium and affiliates, MODEL-AD consortium, external AD researchers

Enhancing AMP-AD Project R01

Increasing resources for target prioritization
within the AMP-AD community

User experience interviews

Understand how our users will interact and utilize the Wall of Targets application - usages, pain points, gaps, and preferences.

Performed think aloud exercise - use the application and state what you are doing and what you are thinking as you use the prototype.

10 participants, including 4 industry/pharma and 3 mouse model system researchers

Version 0, main page

Version 0, detail page

Interviews - what we learned

1. Biological context
2. Nominations and source of evidence
3. Consistency and reproducibility across cohorts
4. Druggability vs. tractability
5. Ranking and comparison

Overview design

Main page, alpha version

Includes overview of evidence for indication of strength of target.

Details page, alpha version

Condensed layout including biological context.

Details page, alpha version

Indication of data sources.

Gene Ontology terms, alpha version

Biological pathways, alpha version

Mouse models, alpha version

Baseline RNA Expression, alpha version

Expression from more sources
and outside of brain.

Search

Enable for nominated targets
(future: whole transcriptome)

Nomination evidence, alpha version

Show evidence from nominating center(s)

Looking forward

• Druggability vs. tractability
• Module-centric search and interaction
• eQTL and genomic variants
• Evidence-based ranking

Evidence-based ranking

AD target explorer: User experience

Rami Al-Ouran, Joshua Shulman, Zhandong Liu
Baylor College of Medicine

AD target explorer: Diagnosis

AD target explorer: Quantitative Neuropathology

plaque mean (MSSM)

Tool also computes simple statistical tests and returns significance.

Thank you